General Pathology Increase stress : Hypertrophy : increase ptn synthesis and gene activation + production of organells like mitochondria

Hyperplasia and hypertrophy occur together except permenant tissues like cardiac myocytes / sk. Ms / nerve Pathological hyperplasia cancer except BPH Decrease stress ? atrophy : decrease cell number : apoptosis Decrease cell size ? ubiquin proteome / Autophagy : lyozomal destruction CHANGE stress : metaplesia Metaplasia occurs by REPROGRAMMING of stem cells , and its REVERSIBLE like GERD Apocrine metaplasia in breast ? NOT PRECANCEROUS ATRA = All Trans Retinoic Acid : for AML Myoscitis ossificans is an example of mesenchymal metaplasia BONE is normal and distinct separation of bone and muscle, NOT osteosarcoma Dysplasia is REVERSIBLE Stress exceeds the cell ability to adapt? INJURY Hypoxia is low oxygen delivery Hypoxemia is low blood oxygen Ischemia decrease BLODD FLOW in artery or vein ( eg: Budd Chiari Synd) MCC of budd chiari is PRV hypercoaggulable state in SLE Any Increase PACO2 like COPD PAO2 will decrease CO : normal PaO2 SaO2 decreased ! EARLY sign of CO is Headache Newborns are susceptible to metHB , Chocolate colored blood + cyanosis Ischemia : 1- damage Na K Pumb 2- failure Ca pump : increase Ca inside 3- anaerobic glycolysis REVERSIBLE = SWELLING : eg : loss of micro villi / membrane blebbing due to swelling / Swelling of RER release of ribosomes decrease ptn synthesis IRREVERSIBLE = membrane damage ( release of enzymes) eg : cardiac enzymes in MI and liver enzymes in LCF Also calcium enters the cells Damage of mitoch membrane and release of cyt.c Calcium and lysozomal enzyme ? = irreversible Cell DEATH ? = Loss of nucleus Necrosis = Large GROUP of cells + Inflammation / Always pathologic not like apoptosis Red infarction : Loosely organized + Blood must RE-ENTER the tissue Liquifactive necrosis ? Enzymes Brain ( by microglial cells) / abscess ( neutrophils enzymes) / pancreatitis ( pancreas itself) NOT fat necrosis surrounding Fat necrosis : Saponification in pancreatitis / breast trauma ( mass : inflammatory response : giant cells fat and calcification)

Saponification : fat + Calcium : example if dystrophic calcification ( like psammoma bodies ) Serum calcium is normal in dystrophic dead tissue Vs. metastatic calcification : calcium or po4 is High .. one of the causes is cancer but metastatic calcification itself is NOT CANCER Fibrinoid necrosis : malignant HTN + Vasculitis 30 yr old with fibrinoid necrosis ? not malignant HTN, not vasculitis : THINK preeclampsia in placental vessels ## Apoptosis energy dependant maybe physiological Dying cells shrink : becomes eosinophilic , apoptotic bodies removed by macrophages Caspasses break CYTOSKELETON activates Endonucleases breaks DNA Fas Ligand bing CD95 (Fas receptor) T cell selection / TNF CD8 + also apoptosis Free radical has an unpaired electron on the outer orbit O O2- H2 O2 OH H2O : one electron at a time radiation hits water in tissue generates free radicals , hydroxyl free radicals is the MOST DAMAGING copper and iron also free radicals : Iron do the Fenton reaction : OH free radical inflammation / acetaminophen Free radicals : Peroxidize the lipids / oxidizes Proteins and DNA (oncogenesis) Elimination of Free radicals : Antioxidants A,C,E / Metal carriers : transferring for Iron and ceruloplasmin for copper / ENZYMES SOD catalase GTH peroxidase CCL4 : in dry cleaning industry CCl3 in P450 in the liver decrease ptn synthesis loss of apolipoproteins FATTY LIVER Reperfusion injury : return of O2 and inflammatory cells = free radicals : in cardai catheterization Amyloid : misfolded protein that deposits in EXTRACELLULAR space (outside) damage Multiple proteins not one kind all are B-pleated sheet configuration Tends to deposit around blood vessels ( see image)

SYSTEMIC AMYLOIDOSIS : Primary amyloidosis : AL chain due to plasma cell dyscriasis : increase Light chain > heavy chain Secondary Amyloidosis : SAA = systemic derived amyloid associated APR chronic inflammation = malignancy / RA / familial mediterranian fever ? FMF : dysfunction of neutrophils : episodes of fever and inflammation involves serosal surface ( pericardium / peritoneum) APR is SAA deposit as amyloid Findings : Nephrotic / restrictive CM / tongue enlargement / HSM / intestine enlargement and malabs REQUIRES BIOBSY from abd fat pad and rectum ( easy to optain )

AMYLOID CANNOT BE REMOVED

LOCALIZED AMYLOIDOSIS : Single organ Non-mutated transthyritin : Senile cardiac : Asymptomatic and 25% in people >80% Mutated ? FAMILIAL AMYLOID CARDIOMYOPATHY : restrictive / African Americans NIDDM excess insulin Amylin which is derived from insulin deposit Alzheimer : AB amyloid protein derived from amyloid precursor ptn present on chr 21 ( early onset) Dialysis ? B2 microglobulin ( in joints) : MHC1 support ## Calcitonin in medullary thyroid : WITHIN tumor biopsy

------------------------Inflammation is due to 1) Infection 2) Tissue Necrosis Goal is eliminate infection OR remove necrotic debris inflammation is Innate : limited specificity Toll like Receptors ? on innate immunity cells : recognize PAMPs [ pathogen associated molecular pattern] : example is CD14 recognize LPS TLR activation up-regulation of NF-kB VD occurs at arterioles , permeability is at capillary end PGE2 FEEEVER and pain Diagram : LTC4 , LTD4 , LTE4 : VC and bronchospasm : increase permeability Mast cells activated by : 1) tissue trauma C3A, C4A , IgE Mast cells : 1) PREFORMED histamine 2) LATE RESPONSE by Leukotrienes C5a , C3a mast cell degranulation C5a chemotactic for PNL , C3b opsonins Hageman factor : from liver : from inflammation : coagulation and DIC Dolor via PGE2 and bradykinin Rubor and calor : from VD : histamine / PGs / bradykinin Tumor : histamine and tissue damage : from post capillary venules Fever : MACROPHAGES : IL1 and TNG increase COX activity In hypothalamus PGE2 increase set point 1) margination : slowing blood flow AT POSTCAPILLARY VENULES 2) Rolling : sialyl lewis x and selectins : P-selectins from Weibel Palade bodies VWF + P-selectin E-selectins : upregulated by TNF and IL-1 3) firm Adhesion : CAM : cellular adhesion molecules bing Integrins on leucocytes CAM : activated by TNF , IL1 Integrins activated by LTB4 and C5a LAD ? lack of CD 18 ni nutrophils to clear the tissue and fascilitate umbilical cord separation delayed

Increased circulating neutrophils ? normally 50% are stuck in the vessels of the lung ( called marginated pool _ , in LAD : marginated pool will be released in the blood Recurrent bac infection that Lack pus bcz no PNL 4) Transmigration : POST CAPILLARY VENULES 5) chemotaxis : C5a IL8 LTB4 and bacterial product 6) Phagocytosis : enhanced by opsonins Pseudopods from neutrophils or macrophage : form Phagosome moves ( in a road of trafficking by microtubules) to fuse with Lysozome Phagolysozome Chediac Higashi : no microtubules no phagolysozomes Nutropenia dt failure of division and cytokinesis Giant granules in leucocytes : piling up bcz they cannot migrate to periphery Defective primary hemostasis : platelets migration Melanocytes : can form pigment , but it cannot be moves to keratinocyes ! ( one melanocyte = 25 keratinocytes) so its partial Peripheral neuropathy : cannot maintain integrity of periphery dt decrease moving 7) destruction of phagocytosed material : oxygen dependant and oxygen independent HOCL bleach is the product of MPO Most bacteria have H2O2 can be used by MPO in CGD Except catalase +ve : destroy H2O2 -ve Nitroblue tetrazolium test : No NADPH = No Blue color MPO deficiency ?? Asymptomatic but maybe candida infection / NbT test is POSITIVE O2 independent : enzymes like Lysozyma and MBP less effective 8) Resolution : PNL die via apoptosis and form Pus 9) the phase of Macrophages ( 2-3 days) via the same ways phagocytosis : PRIMARY MECHANISM is Enzymatic killing by Lysozymes Release cytokines: Resolution by IL-10 and TGF B Continue : IL-8 recruit MORE neutrophils so there maybe ACUTE inflammation for 8 weeks : theres still neutrophils If it cannot handle it ?? summon lymphocytes and chronic inflammation Granuloma = epithelioid histiocytes [ macrophages with abundant pink cytoplasm] NOT NECESSAIRELY : giant cells / rim of lymphocytes Non caseating : foreign material wood breast implant / sarcoidosis / Beryllium in NASA / Crohn / Cat-Scratch ( stellate shaped granuloma ) Caseating Granuloma : do AFP stain look for TB / GMS stain to look for fungus Granuloma = macrophage + TH1 Macrophage secrete IL-12 TH1 Inf gamma convert macrophage to histiocytes SCID : cytokine receptor def / ADA / MHC II Stem-cell transplant ## Brutons :Bacteria / enterovirus / giardia CVID : risk of autoimmune IgA def : especially in celiac diseases

WASP gene = Wiskot Aldrich Syndrome Protein Lebman sacks ? SLE : vegetations on BOTH sides of the valve : characteristic SLE : Pancytopenia FALSLY elevated PTT : the patient is actually hypercoaggulable DVT and Budd chiari / stroke / placental thrombosis Cant chew a cracker dry / dirt in my eye / dental caries : Sjogren Synd Anti-SSA and Anti-SSB : anti Ribonucleoprotein Sjogren associated with RA Sjogren Parotitis risk of B-Cell Lymphoma ## Unilateral swelling late in the disease course Scleroderma ? No peristalsis solids and liquids Serum antibodies against U1 ribonucleoprotein ? MIXED CT DISORDER Healing = Regeneration (same tissue : depend on type of tissues) + Repair ( scar) BM stem cells ? CD34+ Stable tissue : Liver and kidneys Permenant tissue ? ONLY REPAIR by fibrous scar in ms / cardiac / neuron Repair ? permenant tissue / stem cells have been damaged Bone = type one / Cartwolage = type two Regeneration and repait ?? Paracrine signaling FGF ? Angiogenic ## and skeletal development Vit C : important of cross linking between hydroxyl Hypertrophic scar : excess SCAR tissue Keloid : WAYY out of proportion to the wound ear lobe type III

NEOPLASIA Unregulated, irreversible and monoclonal [ proved by G6PD isoforms on chromosome X / androgen receptor isoforms] Polyclonal = hyperplasia Clonality of B cells is by light chain , kappa or lambda ( polyclonal : the K:L is STILL 3:1 ) K:L is 20 : 1 ?? MONOCLONAL lymphoma Both benign and malignant are monoclonal Lymphocytes NO BENIGN Lung cancer is the most killer dt no improvement in screening 30 divisions occur before clinical symptoms With each division mutations more aggressive Depend on site : eg : pancrease is late : worst prognosis Carcinogens are agents that damage DNA Grains in Africa ? aspergillous aflatoxins Arsenic ? Sq cell carcinoma of Skin / Lung cancer cig smoke / angiosarcoma of liver Most important carcinogen in cig smoke is Polycyclic hydrocarbon

Naphthylamine : in cig smoke : urothelial carcinoma of the bladder Nickel lung cancer AML / CML / papillary carc of thyroid : Ionizing radiation hydroxyl free radicals NON-Ionizing radiation ? UVB BCC / Sq cell carcinoma / melanoma Proplem in Xeroderma myc translocated to ON location macrophage eating dying cells starry sky cyclin D Mantle cell lymphoma : G1 S expansion of the mantle : region next to the follicle CDK-4 melanoma Hyperchromasia : increase nucleus The ABSOLUTE DIFFERENCE is that benign tumors NEVER METASTASIZE Immunohistochemistry : antibody that bind the cell to identify it Like keratin / vimentin / .. Used to classify tumors Chromogranin : good : carcinoid / bad : Small cell carcinoma Downregulation of E-Cadherin : attached to laminin and destruct BM BM : collagen 4 + laminin Attach to fibronectin then BV/ lymph Omental cacking : very thick in ovarian cancer

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BLOOD VC of vessel : sympathertic and Endothelin release VWF : Weibel Palade bodies Qualitative ?? NO PETICHIEA ITP = IgG against GP IIB/IIIA Spleen makes antibodies, and they coat platelets, then macrophages ALSO in the spleen eat them Chronic ITP : eg SLE / women in child bearing age ITP : increase magakaryocytes ( to compensate) ADAMTS 13 : cuts down VWF polymer into monomers deficient in TTP ( autoantibodies / autoimmune in adult female ) Abnormal platelet adhesion PLATELET microthrombi E.coli O157:H7 verotoxin damages endothelial cells and damages ADAMTS 13 Qualitative : BSS Glanzman aspirin Uremia decrease function BSS : platelets are lacking GP 1B platelets live shorter mild thrombocytopenia compensatory increased size of platelets Big suckers Coagg factor inhibitor ? usually Abs to factor VIII

Distinguish between hemophalia : mixing study : adding normal plasma : if corrected PTT then its hemophilia not coagg factor inhibitor VWF deficiency : abnormal ristocetin test Desmopressin increase release of VWF from W-P bodies LCF : 1) decrease production of coagg factors, 2) decrease epoxide reductase = decrease activation of Vit K Large volume transfusion = dilution of coagg factors Heparin complex with PF4 forms Abs destroyed fragments can activate other platelets coagulation Adenocarcinoma mucin activate coagg cascade D-Dimer : is the split product of fibrin ( which means there were excess fibrin) Plasmin cleaves Fibrin AND fibrinogen AND /knocks out coagg factors AND block platelet aggregation Radical prostatectomy ?? release of urokinase anticoagg Liver cirrhosis ?? decrease antiplasmin anticoagg Increased fibrinoGEN split products BUT NOT D-DIMERES ( bcz no fibrin ) D_DIMERS is the difference between it and DIC ### ANTEMORTUM CLOT : 1) attached 2) lines of zhan Endothelium releases Heparin Like Molecule HLM Endothelium releases thrombomodulin : modulates thrombin that it can activates protein C ## Vit B12 deficiency can lead to thrombosis dt increased homocysteine Protein C&S deficiency : skin necrosis with warfarin usually knocks out C & S faster and elrllier that 2,7,9,10 , so there will be INCREASED coagg factors coagulation and thrombosis this is why we give heparin In AT III def : you give HIGH DOSES of heparin to activate the limited AT III then give coumarin to maintain and stop heparin then Atherosclerotic embolus : cholesterol crystals picture Caissons diseases = gas embolus causing BONE NECROSIS Amniotic fluid baby skin gets shed off periodically so the amniotic fluid embolus will contain keratin debris and squamous cells ## picture PE is usually silent 1) dual blood supply 2) small and self resolve Symptoms ? 2) large or medium sized artery 2) pre-existing Cardiopulmonary problems ( dual blood supply is not protective ) Spiral CT : vascular filling defects in lung / Doppler in DVT / D-Dimers elevated Hemorrhagic bcz second blood supply blood re-enter / loosely organized tissue Saddled embolus ? saddled to occlude BOTH branches of PA : electomechanical dissociation ( theres contraction bubt no blood is pumped)

ANEMIA: Microcytosis is due to an Extra division to maintain a nice pink cell

Ferroportin is the iron regulator NOT intestinal cells For every 3 TF one carries Iron TIBC : how much TF saturation : how many TF carrying Iron Decrease ferritin \\ always increased TIBC the liver senses and produces more transferring Increased TIBC / BUT decrease saturation INITIALLY normocytic anemia : good RBCs but few of them Pica : psychological drive to get iron : chewing on dirt IDA : INCREASED FEP free erythrocyte protoporphyrin They will give you a lymphocyte to compare size ACD ?? increased ferritin / ergo : decreased TIBC Decrease serum iron / decreases saturation / increase FEP Sideroblastic = decrease protoporphyrin Ringed sideroblast : Iron is present in MITOCHONDRIA Congenital : ALAS def Acquired : Alcoholism ( mitochondrial poison) / Lead ( ALAD and ferrochelatase) / Vit B6 ( ALAS ) High ferritin bcz macrophage will eat all the iron from the sideroblast ( SAME IRON PROFILE as hemochromatosis) Thalassemia carries protection against pl. falciparum Normally 4 alpha alleles on chr 16 Knock out 2 near genes ? cis [ worse] [ in Asians] [ ass with severe thalassemia in offspring] [ high rate of spontaneous abortion] Knock out2 genes opposite ? trans [ less severe] [ Africa] 3 gene deletion ? no problem in foetus after that risk of HbH tetra beta Hb damages RBCs 4 gene deletion tetramer of gamma chain lethal in utero B- thalassemia : alpha tetramers damages RBCs destruction In the spleen NO HBA theres HBA2 and HBF Macrocytic anemia : one less division Hypersegmented neutrophils = greater than 5 lobes Vit B-12 bind to ( R-Binder) from salivary gland Vit B-12 released in intestine by protease of pancrease and bind Intrinsinc factor Complex goes to ileum and absorbed Parietal cells = Proton Pumps / Pink not like blue chief cells / Pernicious anemia Vit B12 def in pancreatic deficiency ? not released from R-Binder Methyl-malonic acid accumulation in B-12 ? neuropathy and SCD Reticulocytes = RNA in cytoplasm A decreased RBCs mass may induce falsly increased Reticulocytes so corrected reticulocytes Corrected = Reticulocytes X hct/normal hct Spleen in normocytic extravascular hemolysis will have hypertrophy

Intravascular ? bing to haptoglobin and send it back to spleen to re-use so decreased haptoglobim but its not enough Hemoglobinemia / Hemoglubinuria / hemosedrinurea tubular cells contain iron die and slough off days over urine Spherocytosis : inherited defects in membrane teathering protein : spectrin / Ankyrin / band 3.1 Increased RDW / parvo B19 crisis Splenectomy : anemia resolves but spherocytes PERSIST / howell jelly bodies HbS POLYMERIZE in acidosis / dehydration / hypoxia this is not covalent binding HbF prevent against sickling so use Hydroxyurea Extravascular hmolyisis / intravascular bcz membrane damage Target cells bcz membrane damage blebs Sickling is usually reversible if irreversible vaso-occlusive crisis Maybe : Acute chest syndrome : occlusion of pulmonary vessels : aggravated by pneumonia classic finding most common cause of death Gross hematuria and ptn urea ? think renal papillary necrosis Sickle cell trait ? 55% HbA and 43% HbS and 2% HbA2 you need MORE than 50% HbS to sicke so they dont sickle but in EXTREME HYPOXIA they can sickle microscopic hematuria eventually decreased ability to concentrate urine Metabisulfite test : screen for HbS : +ve for BOTH trait and diseases HbC LySine PNH : ACQUIRED defect of myloid stem cells ( RBCs / granulocytes / platelets) GPI protein which fixes CD55 (DAF : Decay Accelerating Factor) and CD59 ( MIRL : Membrane inhibitor of Reactive Lysis ) Shallow breathing at night resp acidosis complement activation Sucrose test : SCREEN : activate complement and induce hemolysis MCC of death : thrombosis bcz destruction of platelets fragments activate coagg pathway AML develop in 10% ( its easy to acquire new mutation im myloid stem cells) African G6PD : mild decrease / Mediterranean : marked decrease of enzyme G6PD will not be available for the whole life of RBCs Heinz Preparation ? used to show hemoglobin aggregates SCREENING Bite cells ? macrophages will take a bite with Hb Aggregates Warm IgG antibodies ? lose excess membranes SPHEROCYTOSIS ! SLE / CLL / drugs 1) penicillin : antibody binds to it 2) methyldopa forms antibody IgM ? cold agglutinin fixes complement MAC Mycoplasma / IMN Direct coombs : does the patient has RBC ALREADY coated ? indirect : does the patient have Antibodies in the serum ? Myelophthisic disorder : fibrosis / granuloma / anything that occupies BM

BLOOD CELLS Neutropenia : from drugs Rx is GM-CSF or G-CSF Neutrophilic leukocytosis ? infection / tissue necrosis / cushing Immature neutrophlis in left shift ? decreased CD16 ( which is the Fc receptor) which means they are not functional correctly Eosinophilia ? allergy / parasitic infestation / HODGKINs ?? By IL-5 ## Basophilia ? associated with CML ### Lymphocytes Leukocytosis ? viral infection / Bordetella Pertussis ?? exception bcz it produce Lymphocytosis blocking factor inhibit Lymphocytes from entering LNs remain in the blood Generalized LAD in IMN ? T cells in para-cortex Splenomegaly ? in PALS Atypical lymphocytes : 1) much bigger nucleus than adjacent RBCs 2) abundant blue cytoplasm resemble monocytes Spleen rupture avoid sports for 1 year Rash with PCN Dormancy in B-cells Blast = large / little cytoplasm /punched out nucleus ( nucleolus) MPO crystallize to form Auer Rods marker for myeloblasts tDt is a marker for Lymphoblast ( dna polymerase in the nucleus ) B-ALL CD 10 / 19 / 20 / 22 T-ALL CD2 CD 8 ( NO CD 10 ##) T-ALL Thymic mass lymphoma Teenagers Acute monocytic leukemia ? GUMS ## Acute Megakaryoblastic Leukemia lack MPO Downs Syndrome before the age of Five ## Myelodysplastic syndrome blasts less than 20% with cytopenias CLL : B lymphocytes CD-5 ( normally on T not B ) and CD20 CLL can transform to diffuse large B-cell lymphoma ( enlargement of LNs and Spleen ) In HCL Splenomagealy is due to expansion of RED PULP Dry tap ? bcz BM is fibrosed No LN enlargement ( bcz TRAPPED in BM and in Red bulp) Respond to ADA (-) = Cladribine ( 2-CDA) Adult T-cell Lymphoma theres RASH nad Lytic bone lesions with hypercalcemia ( dont jump to MM) Neoplastic T- cells in epidermis in mycosis fungoides is called Pautrier microabscesses Spread to the blood Sezary syndrome ceribriform nuclei MPD all myeloid cells increase but one in particular increases more Complications 1) hyperuricemia 2)marrow fibrosis 3) transform to acute leukemia

CML BASOPHILS ## In CML the mutation MUST be in a stem cell .. so the mutation maybe in the Myelocytic stem cell AML (2/3) / OR it can be in Hematopoeitic stem cell ALL (1/3) ie : Both can be correct CML chch : 1) LAP negative [ bcz they are inactive] 2) Basophils 3) t(9;22) PRV thrombosis Budd-Chiari PRV : mat cells itching after bathing classic Thrombocytosis : maybe ETC / IDA RARELY leukemia and RARELY fibrosis No significant risk of hyperuricemia just pieces of cytoplasm IMF PDGF Megakaryocytes Splenomegaly and extramedullary hematopoeisis leucoerythroblastic smear no control of size and more immature cells in blood Extramedullary is not sufficient Teardrop stretch as they try to leave BM

LYMPHADENOPAHY Paracortex hyperplasia in viral / follicles in RA and early HIV LNs draining cancer ?? Sinus histiocytosis Lymphoma lymph cells that form a mass Small lymphocytes = well differentiated In follicular lymphoma : the follicles contains cells that may fail somatic hypermutation they need apoptosis but BCL-2 anti apoptotic Translocate from chr 18 to Ig heavy chain on chr 14 Rituximab anti CD-20 Can progress to large B-Cll lymphoma enlarging LN Anti-apoptotic = no macrophages in follicles to clear the failed cells ( no tangible body macrophages Region immediately adjascent to follicle ? Mantle cell lymphoma Marginal zone lymphoma associated with chronic inflammatory state [ hashimoto / sjogren / h,Pylori ] C-myc drives peoduction and growth translocated to Ig heavy chain on chr 14 Diffuse large no follicle or whatever diffuse Sporadically or progressed from follicular B symptoms are due to cytokines ## Nodular sclerosis : neck or mediastinal LNs in females RS cells in spaces lacunar cells Mixed cellularity : EOSINOPHILS called in by IL-5 MM high serum Il-6 often elevated : important growth factor for plasma cells MM activates RANK receptors in osteoclasts

Normal serum ptn electrophoresis : the spike is LESS than Albumin in MM : in SPEP [Serum Protein Electrophoresis] : M spike is higher than Albumin and narrow Usually IgG or IgA Increased IgG decrease charge between RBCs stick together Roleaux formation Primary AL Amyloidosis bcz extra light chain MGUS in elderly may develop MM Waldenstrom macroglobulinemia this Is Lymphoma macro bcz IgM is large Viscocity of the blood increases but no lytic bone lesions or kidney ttt with Plasmaphoresis histiocytosis : CD 1a+ and S100+ peoples name = malignant / malignant = skin rash / 2 people = less than 2 yrs / three people = more than 3 yrs

CVS Intima Endothelium on BM / Media sm.ms / Adventitia : CT Vasculitis : 1) NS symptoms 2)ischemia Ischemia bcz 1)inflammation = tissue factor = thrombosis 2) heal by fibrosis Giant cell arteritis : classically ESR is > 100 Giant cell arteritis : Granulomatous giant cell Its segmental so you do biobsy even if its negative it doesnt exclude Takayasu ? LESS than 50 yrs old Medium vessels = muscular artery supply organs like Renal artery PAN : fibrinoid necrosis fibrosis form NODES String of pearls appearance ? varying stages ( aneurism / fibrosis / aneurism / firbosis / .) A kid with MI ? think Kawasaki Rx ? Aspirin and IVIG NO steroids This is interesting bcz the C/P looks like viral illness and you shouldnt give bcz Ryes syndrome Aspirin bcz inhibits COX and inhibit aggregation and protects them from thrombosis in coronaries P- ANCA = perinuclear anti nutrophils cytoplasmic antibody C-ANCA = cytoplasmic Anti nutrophils cytoplasmic antibody Wagners = Microscopic Polyangitis except : 1) P-ANCA 2) no nasopharynx 3) no granuloma Churg Vs Microscopic both have P-ANCA BUT Churg strauss : 1) eosinophilia 2) granuloma 3) Asthma HSP? IgA deposition in mesangium of kidney

Follows URT infection because it generates IgA ## RAS in old male ? atherosclerosis / in female : Fibromuscular dysplasia Atherosclerosis : Intima of small and large sized vessels Artriolosclerosis : narrowing of small Bl.Vs Monkeberg : Media Rupture atherosclerotic plaque occurs at the neck ## Hyaline artrioloscleorosis : proteins : pink staining ( DM / benign HTN) Glomerular scarring : due to hyaline nephroscleorosis Hyperblastic : smooth muscle hyperplasia flea bitten kidney and ARF Aortic dissection : 1) damage to intima 2) blood goes into media Need per-existing weakening of media and a lot o stress eg : HTN in proximal Aorta HTN = narrowing of vasa vasorum Aneurism sisrbts laminar blood flow activates coagg cascade >5 cm aneurism RUPTURE Triad of ( hypotention / pulsatile abd mass / flank pain) Usually dt atherosclerosis of Abd aorta Angina = REVEERSIBLE injury no necrosis Unstable angina INCOMPLETE occlusion of coronary a. MI : complete occlusion > 20 minutes ( thrombus of pirenzimital ) Fibrinolysis --. Calcium enters the cell contraction bands You only get fibrinous pericarditis with TRANSMURAL infarction Necrisos dark coloration / inflammation yellow / granulation red / fibrosis and scar white Fetal Alcohol Syndrome VSD cri du chat Paradoxical embolus : from Right side ASD Left side PGE : KEEps PDA open TGA meternal Diabetes Infantile coarctation : associated with PDA , occurs proximal to PDA Presented with lower extremity cyanosis / Turner Syndrome Adult coarctation : distal to ductus artriosus : hypotention in low etremitis and bicusbid aortic valve RF = molecular mimicry against M protein and endocardium Erhtyema marginatum : red at the margins Scarring of the valve fish mouth appearance RHD Vs wear and tear AS stenosis : 1) in RHD theres ALWAYS MS 2) RHD theres fusion of the valves pulmonary congestion hge macrophages HF cells are in the lung septic embolization in SBE jenway and osler / ACD Trans-eophageal-echo -> TEE : see vegetations in SBE Sterile vegetations hypercoagg state or adenocarcinoma Libman sacks ? MV regurgitation DCM regurgitations stretch of rings / arrhythmia stretch of conducting systems

GI : -

DCM pregnancy Myocarditis can cause DCM Ttt : Transplant only Congenital HOCM -- > AD : genetic mutations in sarcomere proteins HOCM : myocardial fibrils with disarray RCM = CHF blood accumulated backwards Heart is permenant cells , so the only tumor is mesenchymal myxoma Rhabdomyoma is a hamartoma Metastasis is more common than primary tumors pericardium pericardial effusion

Behchet syndrome : apthus ulcers + genital ulcers after viral infection : no etiology known Hairy leukoplakia ? on the lateral side NO dysplasia True leukoplakia is dysplasia vs candidiasis : scrab test Erythroplakia : vascularized leukoplakia [ more suggestive to dysplasia] Pleomorphic adenoma = stromal + epithelial MW syndrome : painful hematemesis Esoph varices ? painless hematemesis : MCC of death in cirrhoso [ with DIC] Chronic gastritis is type IV HPY , pernicious anemia is type II HPY !!!!! Celiac disease : DQ2 and DQ8 Celiac is IgA deficient because its deposited and form dermatitis EATL : enteropathy associated T cell lymphoma : associated with celiac pANCA : think about UC smoking increases risk of chrons and protects from UC RECTAL SUCTIO BIOBSY : not normal mucosal biobsy in hirchsbrung . to be able to truly look at ganglia Aspirin : decrease COX , decrease adenoma carcinoma sequence Sessile is more dangerous and villous is more dangerous Pancreas : Liquifactive necrosis + fat necrosis of the surrounding adipose tissue Hypocalcemia dt use of calcium in saponification Pancreatitis Shock dt digestion of Bl.Vs hge and shock Chronic pancreatitis ? no elevated enzymes all cells are destroyed Pancreatic adenocarcinoma DUCTAL carcinoma

Thin elderly male that suddenly developed DM ? think cancer pancreas Estrogen stimulate HMG coA reductase / increase LPL receptors in the liver Gall bladder to the right scapula Biliary colic is dt contraction of GB on an obstructed duct Phototheraby doesnt conjugate bilirubin, it just makes it soluble Viral hepatitis : UCB increase dt damage of hepatocytes / CB increases dt damage of bile ductules Acute hepatitis : hepatic lobules / chronic hepatitis ? portal tracts Fibrosis in cirrhosis by TGF-beta from stellate cells Coagulopathy in cirrhosis ? decrease activity of epoxide reductase Mallory bodies are damaged intermediate filaments in hepatocytes Hemochromatosis : brown pigment in hepatocytes DD : lipofuscin : wear and tear pigment / iron do Prussian blue Wilsons : inability to incorporate copper in ceruloplasmin / cant put it into bile build in hepatocytes free radicals Primary sclerosing cholangitis : peri-ductal fibrosis with onion-skin [ figure] P-ANCA / UC association ## Hypoglycemic child , elevated LFTs , N, V : check history for Reyes Rupture adenoma bcz its subcapsular Aspergilous aflatoxins mutations in P53 mutations ## HCC vein increase risk of budd chiari Nodular free edge of liver ? metastasis

REPRODUCTIVE unilateral lesion in the side of the vulva adjascent to vaginal canal bartholin cyst painful HPV vulva / vagina / cervix = lower tract HPV : low risk = condyloma 6/11 HPV high risk = Dysplasia and carcinoma 16/18/31/33 Risk is due to DNA sequence [ DNA virus ] Lichen sclerosis : parchement like vulva postmenauposal women BENIGN slightly increased risk of sq cell carcinoma Lichen simplex chronicus opposite : hyperplasia of sq epithelium dt chronic irritation and scratching BENIGN NO increased risk Sq cell carcinoma in vulva resembles leukoplakia do biobsy Maybe HPV related VIN carcinoma 16/18 /3 1 / 33 Non HPV long standidn lichen sclerosis [ elderly women larger than 70 yrs ] Extramammary pagets diseases : malignant epithelial cells in the epidermis

DD : carcinoma Vs. Melanoma do stains Pagets Pas +ve / Keratin +ve / s100 ve Melanoma PAS ve / Keratin ve / S100 +ve ONLY epithelial cells make mucus and PAS +ve ## Pagets diseases in the nipple usually theres a cancer in the breast Vulva ? usually NO cancer in the lower genital tract Adenosis ; persistence of columnar epithelium in the lower part of the vagina ## DES use These women are high risk for celar cell adenocarcinoma Mass protruding from vagina / penis child think rhabdomyosarcoma [ picture] Malignant cell is Rhabdomyoblast 1) cytoplasmic cross-straiation / +ve for Desmin or Myoglobim ## VAIN ? vaginal intraepithelial neoplasia ( Vs VIN : vulvar ) HPV infection cleared by immunity only PERSISTENT infection with HIGH risk may do CIN High risk ? produce E6 [ X p53] and produce E7 [ X Rb ] Rb bing E2F no Rb ? E2F free progression of cell cycle Cervical carcinoma : bleeding or pain after intercourse Immunodeficiency is highly associated with high risk HPV [ AIDS defining lesion ] Cervix : squamous AND adeno are possible , however squamous is more common , but BOTH can occur and BOTH are related to hPV Cerial cancer may invade through uretine wall into bladder / ureter and for hydronephrosis PAP smear is sensitive colposcopy is specific THEN Biobsy PAP smear is at transformation zone ## PAP doesnt detect adenocarcinoma as well ## much more difficult to detect The prevalence of cervical ADENOcarcinoma has not reduced , only squamous ## Quadrivalent vaccine 6/11/16/18 5 yrs protection PAP smears are still uses other strains ## Endometrium : functionalis layers sheds , Basalis persitis regenerates Asherman syndrome damage to basalis eg by excessive D&C DUB ? anovulatory cycle : proliferative phase no secretory phase no shedding - another proliferative phase on top of the last one cells grow beyond blood supply necrosis and dysfunctional bleeding Endometritis retained parts of the placenta Chronic endometritis have to see plasma cells Endometrial polyp : protrusion of endometirum : result of Tamoxifen bcz its agonist on the breast Endometriosis : (((GLANDS + STOMA ))) Endometriosis increases the risk of carcinoma at the site of endometriosis especially at the ovary ##

Endomatrial hyperplasia unopposed estrogen : GLANDS ONLY relative to the stroma ## Endometrioid ? the cancer endometrium looks pretty much like the normal endometrium usually from the hyperplastic endometrium usually in age of 50 OTHER type is sporadic : from atrophic endometrium papillary serous ## occur in elderly ## p53 mutation Psammoma bodies may arise in sporadic type Leiomyoma is realted to Estrogen and shrinks after menopause Multiple is MOSTLY benign NOT leiomyosarcoma White whorly masses and multiple and Pre-menopause : benign Vs he and necrosis and single nad post menopause Leiomyomas are asymptomatic ( may be bleeding / infertility / pelvic mass ) Leiomyosarcoma : De-novo NOT from leiomyoma Post menopausal not like leiomyoma SINGLE lesion with he and necrosis mitotic activity and cellular atypia maybe hge in CL CL hgic cyst Ovarian tumors : epithelial / sex cord / germ cells Surface Epithelial : Present LATE , and vague symptoms CA-125 (35-40) benign (60-70) malignant 1) Cystadenoma : flast lining of the cells : single layer ( serous / mucinous ) 2) Cystadenocarcinoma : multiple complex cysts and shaggy lining not smoothe ( serous / mucinous ) cells invade into cT post menopausal women BRCA 1 mutation serous carcinoma of the ovary / fallopian tube also ## 3) Border line tumors : but metastatic potentials 4) Endometrioid histology : usually malignant , 50% have separate carcinoma in the endometrium as well : check there 5) Brenner tumor : Bladder like Germ cell Reproductive age ( 15-30 ) 1) Fetal tissue : Cystic teratoma Benign , except of 1) immature teratoma ( usually neuro ectoderm) 2) if the tissue contains cancer itself [ somatic malignancy] struma ovarii : contains thyroid tissue : THrx with mass In the ovary 2) Fetal tissue : Embryonal carcinoma : primitive and aggressive with early metastasis

3) Germ cells : Dysgerminoma : oocytes : large cells with central nuclei Most common type , resembles seminoma LDH tumor marker 4) Yolk sac : Endodermal sinus tumore MC in kids produces AFP schiller duval bodies : glomerular like 5) Placental : Choriocarcinoma NO VILLI just the trophoblast EARLY HGIC spread : programmed to invade poor response to chemo ?? ## Sex-Cord resemble granulose and theca cells ( vs : Leydig and sertoli ) 1) Granulosa theca cell tumor : produces Estrogen : usually in child with precocious puberty / adult with heavy menses / elderly with postmenopausal tumor 2) Sertoli-Leydig cell tumor ? may develop in female dt common origin - contain Reinke crystals : pink cells with crystals produce androgen 3) Fibroma : fibroblasts meigs syndrome Metastasis 1) Kruckenberg tumor : Classically but not only : Gastric cancer diffuse type : signet ring cells ( maybe breast in lobular carcinoma colon cancer ) mucinous tumor ? ask if its primary or metastatic one ovary : more likely primary / both ovaries : metastatic 2) Pseudomyxoma peritonei : mucin within peritoneum : jelly belly usually a tumor within the appendix metastasize to the ovary [ appendix / ovary / peritoneum ]

MC site in ectopic pregnancy : fallobian tube dt scar 1) PID 2) endometriosis lower quadrant Abd pain weeks after missed period vaginal bleeding / cramp pain / pass fetal tissues placenta previa : preview of the placenta preeclapsia is realted mainly to placenta fibrinoid necrosis in placental vessels SIDS : 1 month to 1 year : usually during sleep Snow strom in hydatiform mole ? bcz grape masses full of fluid : black and white Complete mole : Completely molar with no fetal Completely involves the villi

Compeletely involves ALL the villi Complete risk for carcinoma Choricarcinoma 1) complication of gestation or mole or even normal preg 2) SPONTANEOUS germ cell tumor Gestational way responds well to chemo , BUT germ cell tumor NOT RESPONSIVE to chemo ## HY

Penis Hypospadius : failure of fusion of urethral folds Epispadius : abnormality of genital tubercle Orchitis : Chlamydia D-K / NG in child E.coli and pseudomonas Mumps Autoimmune ( DD TB : acid fast and necrotizing granuloma) Torsion : twist of the cord : artery patent vein collapsed : blood get in but no out --? Hgic infarct Adolescent with sudden onset and absent cremastric reflex Testicular tumors : only SC or Germinal Testicular tumors are NOT biobsied 1) it will seed to scrotum 2) mostly Germ cell tumors and are malignant Germ cell tumors : Seminoma and non seminoma Seminoma : large cells with clear cytoplasm and central nuclei = dysgerminoma Mass is homogenous with no hge or necrosis May produce HCG Embryonal carcinoma : hge and necrosis CTX may result in differentiation AFP or HCG Yolk sac tumor AFP and shiller duval body glomeruloid like Choricarcinoma B-HCG : resemble TSH so can cause hyperthyroidism You dont get villi : only trophoblasts Tiny mass is primary and metastasis is large against logic Teratoma AFP or B-HCG Mixed Prognosis upon the worst Sex cord

Leydig cell produce androgen and precocious pubery Reinke crystals Sertoli cell tubules clinically silent Testicular tumors : 15-40 : germ cell 95% / >60% is lymphoma Prostatitis = orchitis organisms BPH may cause blebing of the bladder PSA is elevated : produced by glands : extra glands ? slight elevation 5-alpha reductase take months Prostatic adenocarcinoma clinically silent bcz its peripheral and post away from urethra so no obstruction Screen by DRE / PSA from 4-10 or higher Gleason grading : architecture alone not nucleus : the higher score the worse prognosis

ENDOCRINE In prolactinoma : no galactorrhea in males bcz they have no sufficient glandular tissue and lobules Octeriotide : blocks response of Ant Pit to GHRH Sheehan : no lactation / loss of Pubic hair dt loss of Androgen bcz no LH Empty sella : herniation of SAH into sella leading to death of Ant pituitary SIADH : Hyponatremia and mental changes ( vs water deprivation ) Thyroxin : hyperglycemia Graves : woman in child bearing age Graves diseases : scalloping of the colloid : space between colloid and the edge of the follicle Thyrotoxicosis : my use steroids to maintain the circulation Dyshormogentic goiter ? deficiency in Peroxidase enzyme ( mostly ) hypothyroidism Myxodema GAG deposition in the larynx deep voice and tongue Hashimoto : destryoy thyroid follicles some will leak into the blood giving hyperthyroidism , then goes back to normal and less than normal Hashimoto : antithyroglobulin and anti microsomal Germinal centers form marginal zone may develop lymphoma Hurthle cells : large cells with eosinophilic cytoplasm Subacute granulomatous thyroiditis : tender and NO hypothyroidism Reidel : maybe fibrosis of local structures Reidel ? young patients / Old age ? anaplastic carcinoma Radioactive I increased in nodular goter or graves / decrease in carcinoma or adenoma Then DO FNA , not true cut biopsy bcz its very bloody Follicular carcinoma ALSO has a capsule BUT carcinoma invade the capsule

FNA cannot distinguish MUST see the capsule ## Follicular carcinoma like blood metastasis Ret mutation ? prophylactic thyroidectomy PTH activates osteoblasts which in turn activated osteoclasts ## Hyperpara MCC parathyroid adenoma Hyperpara hypercalcemia enzyme activator pancreatitis ## High PTH osteitis fibrosa cystic Why ALP elevation when you bone resorbtion ? bcz it first activates osteoBlasts Pseudohypopara : KKDD , proplem in Gs protein hypocalcemia with increased PTH DM : hyperkalemia but low total potassium bcz its escreted in urine So ttt : replace potassium Osmotic damage : schwan cells / pericytes of retinal bl vs he / lens Cushing : gluconeogenesis : high glucose : excess insulin : increase fat storage on face / trunk / back Htn bcz upregulated alpha-1 reeptors Sac of blood adrenal : waterhouse fridrichson syndrome Lung cancer lovers to go to the adrenal

BREAST Breast develop in the milk line ( from axilla to vulva) can develop anywhere TDLU : Terminal duct lobule unit : Functional unit : lobule secrete , ducts deliver Duct and lobules : inner luminal layer and outer myoepithelial layer Breast is hormone sensitive : develop after menarche / tenderness during menses / hyperplasia in pregnancy / atrophy after menopause Galactorrhea is not realted to breast cancer Acute mastitis : staph dt fissures due to lactation Continue drainage continue to feed the child and use dicloxacillin Pericuctal mastitis : subarelolar duct inflammation / usually in smokers bcz loss of vit A and loss of speciality of epithelium / sq metaplasia and keratin plugs the duct / inflamataion fibrosis and nipple retraction [ vs breast cancer ] Mammary duct ectasia : inflammation of the wall of duct dilatation [ ectasia ] green brown nipple discharge and maybe a mass multiparous post menopausal woman [ vs cancer ] Biopsy : chronic inflammation and plasma cells Fat necrosis : maybe minor trauma and biopsy show calcifications and giant cells Fibrocystic change : pre-menopausal women change : bcz its related to changing hormonal levels cysts are blue in color : blue domed appearance ##

BENIGN NO RISK OF CANCER : fibrosis / cyst / apocrine metaplasia [ this is an exception of metaplasia : no cancer risk] some carry risk of INVASIVE CARCINOMA IN BOTH BREASTS ? * ductal hyperplasia : excess number of cells [ X2 risk ] * Sclerosing adenosis : too many glands + fibrosis and hardening often calcified [ X2 risk ] * Atypical hyperplasia : Atypical cells in ducts / or in lobules : ductal or lobular hyperplasia [ X5 risk ] Intra ductal papilloma : benign variant has BOTH layers : epithelial cells and myoepithelial cells post menopausal woman with bloody nipple discharge papillary carcinoma ?? NO myoepithelial cells ## Fibroadenoma : most common tumor in premenopausal women wel demarcated and mobile Phyllodes : similar to fibroadenoma but overgrowth of the fibers and leaf like projections [ post menopausal women can get cancer ] Cancer : first degree relative : sister / mother / daughter DCIS only in the duct walks its way into the terminal duct and the nipple ? Pagets disease Invade invasive ductal carcinoma LCIS invade = invasive lobular carcinoma DCIS : no mass detected as calcification on top of dead cells [ vs fat necrosis / sclerosing adenosis ] Pagets disease of the breast THERE WILL be a cancer somewhere in the breast INVASIVE DUCTAL : tubular : tubule like structures with ONE layer and Desmoplastic stroma 9 CT supporting the tumor) good prognosis bcz tumor cells a re bound by stroma mucinous : good prognosis bcz malignant cells bound by mucus inflammatory : looks like infection and acute mastitis but not responsive by antibiotics [[ see after 10 days ]] cancer in dermal lymphatics ( must see clinical and EM ) poor prognosis bcz its already seeding Medullary carcinoma : high grade [ in BRCA1 mutations] LCIS by chance : no mass or calcification lacks E-cadherin : so cells are separated or not attached to each other due to mutation of cadherin gene usually multifocal and bilateral use Tamoxifen low risk for development of invasive INVASIVE LOBULAR invade in SINGLE file pattern [ single from each other bcz no E-cadherin ] NO ductal

structures ## Metastasis is most important, but most patients dont appear with metastasis , so most useful is Nodal affection Sentinel : inject dye and see the 1st LN affected not to remove NORMAL LNs HER 2 neu is a cll SURFACE Estrogen is cytoplasmic that goes to the nucleus Tripple negative ( ER / PR / HER 2neu ) poor prognosis BRCA 2 breast cancer in males Male : usually ductal carcinoma bcz no lobules aslan BRCA2 and kleinfilter

CNS NTD : low folate PRIOR to conception Syrngomyelia : P/T on both sides may be LMNL if expands maybe lateral horn and horners syndrome Familial ALS ? Zinc copper superoxide dismutase mutation Meningitis is inflammation of leptomeninges : ie pia and arachnoid Bacterial meningitis : PUS may press on the brain causing herniation Cerebral Vascular diseases : Global cerebral ischemia : mild ( conusion like in insulinoma ) severe ( vegetables ) moderate ( infarcts and watershed area) laminar necrosis : present in lines [ cerebellum or hippocampus ] Ischemic stroke : Thrombotic PALE infarction at the periphery [ bcz you cannot lyse the thrombus it will reform ] Embolic : when embolus gets lysed hgic infarction Lacunar : hyaline arteriolosclerosis in small Bl.vs deep areas Intracerebral hge : rupture charcot bouchard aneurism SAH : berry anurism lack media layer in branching point ## MLD cannot degrade mylin acumilate in lysozomes Adrenoleukodystrohpy : demylinating diseases : failure of adding coA to long chain fatty acids fatty acids accumulate and damage adrenal gland and white matter JC virus immunodeficiency activates it PMLE Apo E4 increase risk of beta amyloid [ 4 >2 ] Apo E2 decreased risk of Beta amyloid

DS ? APP is present on chromosome 21 , they have extra chr 21 and extra APP Familial : presinillin 1 mainly mutation ( also presinillin 2 ) Brain atrophy ? ventricles dilate to fill the space Ex Vaco A-Beta amyloid may deposit on blood vessels of the brain Amyloid angiopathy TAU protein : hyperphosphorylated cannot organize microtubules neurofibrillary tangles Vascular dementia : damage of brain areas ( 3,5,6 pyramidal neurons and hippocampus ) 2nd MCC of dementia MPTP can result in Parkinsons Parkinsons dementia ? LATER not EARLY Early ? Lewy bodies in cortex lewy body dementia not parkinsons Striatum ? it got a striate running in between ( internal capsule ) Anticipation ? further expansion of tnr in SPERMATOGENESIS LP improves normal pressure hydrocephalus increased CSF bcz decreased absorbtion of CSF in arachnoid villi [ unknown reason] stretch corona radiate Prion ? beta pleated sheets How can you get beta pleated ptn ? sporadic / inherited / Transmitted [ CJD : ( maybe corneal transplant ) RAPID dementia and patient die within a year + startle myoclonus [ involuntary ms contraction wit minimal stimuli ] and ataxia / spike wave complexes on EEg ] Variant CJD ? mad cow Familial fatal insomnia ? inherited with exaggerated startle response 50% Glial cells : atrocytes oligodendrocyes ependymal cells 50% neurons + meningothelial cells Meningeoma : female > male bcz its related to Estrogen Compresses but doesnt invade Medulloblastoma Drop metastasis : to spinal cord

MSK Activating mutation in FGF3 inhibit cartilage OI : blue sclera : exposure of choroidal veins Acidic environment is necessary to remova Ca from bone ## CA is required to produce acid CA deficience ? in osteopetrosis : failure of resorbtion Tie in with RTA ## Alkaline environment is required to add Ca to bone ( Alk phosphatase ) Pagets disease starts by osteoclasts Lytic bone surrounded by sclerosis osteomylitis Osteoma : fascial bone / Gardner Syndrome

Osteoid osteoma : osteoblasts tumor surrounded by active bone Diaphysis of long bone cortex of long bone bone pain resolves with Aspirin Osteoblastoma : vertebra pain doesnr respond to ASA Chondroma : small bones of hands and feet Chondrosarcoma : pelvis or femur Pannus is inflamed granulation tissue in RA [ bl vs / fibriblast / myofibroblast] Myofibroblasts contract causing deformities Systemic manifestaions Dermatomyoscitis : may get malar rash Dermatomyoscitis : Perimysium inflammation with perifascicular atrophy of the muscle Polymyoscitis : no skin Endomysial inflammation Dystrophin links cytoskeleton to extracellular matrix CK is elevated in Duchene dt damage of ms fibers Lambert-Eaton : Improves with ms use Eyes are spared Anticholinergics are of no use Resolves with resection of cancer Rhabdomyosarcoma : desmin positive and rhabdomyoblast Stratum spinosum : DESMOSOMES Acne : hormone related increase in sebum excess keratin block the follicle ( comedones) Probionibacterium acnes : infection of acne : use benzoyl peroxides antimicrobial Psoriasis : associated with HLA-C acanthosis : increase spinosum and epidermal hyperplasia Parakeratosis / neutrophils in coneum : munro abscess / elongated paplillae with thinning above them , exposure of bl. Vs [ asupitz] Ttt : steroids + PUVA : psoralin + UVA Lichen planus : Pruritic papules, purple , polygonal , planar Inflammation of dermal epidermal junction sawtoothe appearance wicham stria associated with hep c Pemphigus : basal cells is intact Wall of blister rupture easily bcz not all layers over blisters Separation bcz IgG gainst desmoglein component of desmosome separation : Acantholysis of strarum spinosum Immunohistochemistry :IgG surrounding keratinocytes fishnet appearance ##

Bullous pemph : not rupture easily wall is entire epidermis oral mucosa is spared Dermatitis herpetiformis : resembles little blisters of herpes IgA deposits ( against gluten ) Erythema multiforme : mycoplasma / HSV / malignancy Target lesion : necrosis of center EM + oral mucosa + fever = SJS Severe SJS = TEN drug with sloughing of skin Pseudocysts in seborrhic keratosis : contains pink keratin ## coin like stuck on lesions Vitiligo autoimmune destruction of melanocytes In lighter individual ? failure to tan Albinism : Melanocytes are normal problem with tyrosinase Freckles darker in sun lightdt increase number of Melanosomes NOT melanocytes [ organelle in melanocytes ] Melasma : mask like pigmentation of cheeks : pregnancy Nevus have hair mostly, but melanoma destroys skin and hair follicles Acquired nevus starts in a child as Junctional then progresses to dermis [ compound] then junctional disappears and remains the intradermal [ most common in adults ] Lentigo maligna : lentiginous means remain in d-epidermal junction excellent prognosis Superficial spreading : good prognosis Nodular melanoma : Early vertical phase push epidermis up nodules Acral lentiginous palms and soles not related to sun black people Scalded skin syndrome : separation is at stratum granulosum : very superficial Vs TEN : dermal epidermal junction very deep

NUTRITION

Kwash : liver ptn decrease , muscle ptn is relatively unchanged Anorecia / bullemia : MCC of death is Vfib dt hypokalemia In hyervitaminosis A : skin is yellow but sclera is normal unlike jaundice Alkalinephosphatase dephosphorylates pyrophosphate which normally inhibits bone mineralization Epoxide reductase activates vitamin K Bitots spots in Vit A deficiency

High fiber diet : decrease Estrogen deconjugation / binds lipocholic acid which colon cancer / increase fecal bacteria in fermentable type / increase stool freq

Renal : Unilateral renal agenesis : later on life theres hyper filtration syndrome and Renal failure Dysplastic kidney ? cysts with wall containing cartilage : NON INHERITED !! dont confuse with ADPKD Medullary cystic : shrinken kidnys + cysts in MEDULLA Most important in interstitial nephritis is eosinophilic cell casts Very important : in MCD there is effacement of foot processes because of cytokines, in Hodgkins Lymphoma theres a huge amount of cytokines which is responsible for the B symptoms such as fever, night sweats, in type II MPGN : theres antibody to C3 convertase which decrease serum C3 and increase c3a and c3b DM nephropathy ? NEG of efferent, so ACEi decrease it and good prognosis Bladder cancer : 2 pathways : Papillary pathway: start LG HG invade Flat pathway : start HG invade + EARLY p53 mutation Bladder adenocarcinoma ? urachal remnants at the dome of the bladder Cystitis glandularis : cystitis followed by metaplasia Bladder esxtophy

Respiratory : Nasal polyps : allergic rhinitis / Cystic fibrosis / Aspirin intolerance Angiofibroma : in adolescent males : epistaxis African children and Chinese young adult : EBV NP carcinoma : epithelial cells [keratin] on a background of lymphocytes Laryngotracheobronchitis : parainfluenza virus Vocal cord nodules : degenerate myxoid tissue : singers Laryngeal papilloma is single in adult , multiple in children [ hpv] LOW risk of carcinoma TB meningitis ? BASE of meninges Smokers : cenrtiacinar emphysema in upper lobes Alpha-1 antitrypsin deficiency : accumulation of unfolded protein in liver ER ## [picture] PiM is normal allele , PiZ is the mutant Heterozygotes ? normal except if smoking Homozygote : panacinar + cirrhosis They will NOT have mucus cough Very thin patients

IL-5 calls in eosinophils Bronchiactasis : Amyloidosis TGF-B induce ILF Beryllium : In miners / aerospace NASA : non-caseating granuloma in the lungs and hilar LNs, various organ : NOT SARCOIDOSIS :Berryliosis Sarcoidosis ? lacrimal and salivary glands : mimic sjogrens Insulin inhibit surfactant in GDM Free radicals : ROP + damage to the lung with bronchopulmonary dysplasia Sq cell carcinoma : keratin pearls / Intercellular bridges Broncioloalveolar cell carcinoma : clara cell tumour , consolidation like on imaging , LM [ pic] excellent prognosis Lung loves to metastasize to adrenal gland